Neuroprotective evidence of alpha-lipoic acid and desvenlafaxine on memory deficit in a neuroendocrine model of depression.

Cognitive impairment is present in patients with depression. We hypothesized that alpha-lipoic acid (ALA) can reduce cognitive impairment, especially when combined to antidepressants. Female mice received vehicle or corticosterone (CORT) 20 mg/kg, s.c. for 14 days. From the 15th to 21st day, the animals were divided in groups: vehicle, CORT, CORT+desvenlafaxine (DVS) 10 or 20 mg/kg, ALA 100 or 200 mg/kg, DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Tail suspension (TST), social interaction (SIT), novel object recognition (NOR), and Y-maze tests were conducted. Acetylcholinesterase activity (AChE) was measured in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). CORT caused depressive-like behavior, impairment in SIT, and cognitive deficits. Alpha-lipoic acid and DVS, alone or combined, reversed CORT effect on TST. In the NOR, ALA200 alone, DVS10+ALA100, or DVS10+ALA200 reversed the deficits in short-term memory, while DVS20 alone or DVS20+ALA200 reversed the deficits in long-term memory. In the Y-maze test, ALA200 alone, DVS20+ALA100, or DVS20+ALA200 reversed the deficits caused by CORT in the working memory. CORT increased AChE in the PFC, HC, and ST. ALA200 alone or DVS20+ALA200 reversed this effect in the PFC, while DVS20 or DVS20+ALA100 reversed this effect in the HC. In the ST, DVS10 or 20, alone or combined, and ALA100 reversed the effects of CORT. These results suggest that DVS+ALA, by reversing CORT-induced memory and social deficits, seems to be a promising therapy for the treatment of depression and reversal of cognitive impairment observed in this disorder.

Evidence for protective effect of lipoic acid and desvenlafaxine on oxidative stress in a model depression in mice.

Oxidative stress is implicated in the neurobiology of depression. Here we investigated oxidative alterations in brain areas of animals submitted to the model of depression induced by corticosterone (CORT) and the effects of the antioxidant compound alpha-lipoic acid (ALA) alone or associated with the antidepressant desvenlafaxine (DVS) in these alterations. Female mice received vehicle or CORT (20 mg/kg) during 14 days. From the 15th to 21st days different animals received further administrations of: vehicle, DVS (10 or 20 mg/kg), ALA (100 or 200 mg/kg), or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Twenty-four hours after the last drug administration prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were dissected for the determination of the activity of superoxide dismutase (SOD), reduced glutathione (GSH) and lipid peroxidation (LP) levels. CORT significantly increased SOD activity in the PFC and HC, decreased GSH levels in the HC and increased LP in all brain areas studied when compared to saline-treated animals. Decrements of SOD activity were observed in all groups and brain areas studied when compared to controls and CORT. The hippocampal decrease in GSH was reversed by ALA100, DVS10+ALA100, DVS20+ALA100 and DVS20+ALA200. The same DVS+ALA combination groups presented increased levels of GSH in the PFC and ST. The greater GSH levels were observed in the PFC, HC and ST of DVS20+ALA200 mice. LP was reversed in the groups ALA200 (PFC), DVS10+ALA100, DVS20+ALA100 (PFC, HC and ST), and DVS20+ALA200 (PFC, HC). Our findings contribute to the previous preclinical evidences implicating ALA as a promising agent for augmentation therapy in depression.

Reversal of corticosterone-induced BDNF alterations by the natural antioxidant alpha-lipoic acid alone and combined with desvenlafaxine: Emphasis on the neurotrophic hypothesis of depression.

Brain derived neurotrophic factor (BDNF) is linked to the pathophysiology of depression. We hypothesized that BDNF is one of the neurobiological pathways related to the augmentation effect of alpha-lipoic acid (ALA) when associated with antidepressants. Female mice were administered vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days the animals were divided in groups that were further administered: vehicle, desvenlafaxine (DVS) 10 or 20mg/kg, ALA 100 or 200mg/kg or the combinations of DVS10+ALA100, DVS20+ALA100, DVS10+ALA200 or DVS20+ALA200. ALA or DVS alone or in combination reversed CORT-induced increase in immobility time in the forced swimming test and decrease in sucrose preference, presenting, thus, an antidepressant-like effect. DVS10 alone reversed CORT-induced decrease in BDNF in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST). The same was observed in the HC and ST of ALA200 treated animals. The combination of DVS and ALA200 reversed CORT-induced alterations in BDNF and even, in some cases, increased the levels of this neurotrophin when compared to vehicle-treated animals in HC and ST. Taken together, these results suggest that the combination of the DVS+ALA may be valuable for treating conditions in which BDNF levels are decreased, such as depression.

Central effects of lipoic acid associated with paroxetine in mice.

Antidepressants, including selective serotonin reuptake inhibitors, are commonly prescribed for the treatment of affective disorders such as anxiety and depression. The purpose of this study was to investigate the central effects of acute administration of paroxetine (PXT) combined with lipoic acid (LA) on various behavioral models in mice. Paroxetine (10 and 20 mg/kg), LA (100 mg/kg), or vehicle was administered, intraperitoneally, 30 minutes before the tests. The results showed that PXT (10 mg/kg) alone and in combination with LA increased locomotor activity. In the anxiety models studied, an anxiolytic effect was observed after the administration of LA and PXT. In the tail suspension test, PXT at both doses and in combination with LA caused a significant decrease in immobility time. These results indicate possible anxiolytic and antidepressant effects of LA associated with PXT. These data suggest that coadministration of LA and PXT may improve anxiolytic and antidepressant responses, and being more effective than each drug alone. However, further studies are necessary to investigate the mechanism by which antioxidants exert antidepressant or anxiolytic action.

Augmentation therapy with alpha-lipoic acid and desvenlafaxine: a future target for treatment of depression?

This study was designed to investigate the possible antidepressant effects of the antioxidant alpha-lipoic acid (ALA) as a stand-alone treatment or in association with desvenlafaxine (DVS) in the chronic corticosterone (CORT)-induced depression model. The depression model was induced by repeated administrations of CORT (20 mg/kg, subcutaneous) in mice over a period of 14 days. Between days 15 and 21, a randomized group of mice received DVS (10 or 20 mg/kg, per os [PO]), ALA (100 or 200 mg/kg, PO), or a combination of DVS (10 or 20 mg/kg, PO) and ALA (100 or 200 mg/kg, PO) along with the CORT injections for the remaining 7 days. Other groups of mice received DVS (10 or 20 mg/kg, PO) or ALA (100 or 200 mg/kg, PO) alone. Open field test, elevated plus maze (EPM) test, tail suspension test (TST), and forced swimming test (FST) were carried out 1 h after the last injection of CORT. Repeated CORT injections induced anxiety-like and depressive-like behaviors as observed by decreased open arms entries in the EPM test and increased immobility time in the TST and FST. The administration of DVS and ALA alone was able to reverse the increases in the immobility time. The combination of ALA and DVS potentiated the observed effects of DVS. These results suggest that augmentation therapy with the addition of antioxidant drugs may be an important pharmacological approach for the treatment of depression.

Anticonvulsant action of Calotropis procera latex proteins.

Calotropis procera (Ait.) R.Br. is a laticiferous plant belonging to the Apocynaceae family. C. procera latex proteins were evaluated with respect to anticonvulsant and sedative activity in mouse models of pentylenetetrazol (PTZ)-, pilocarpine-, and strychnine-induced convulsions or turning behavior and pentobarbital-induced sleep. In the strychnine- and pilocarpine-induced seizure models, C. procera latex proteins caused no significant alterations in latencies to convulsions and death, as compared with controls. In the PTZ-induced seizure model, administration of C. procera latex proteins in high doses (50 or 100mg/kg) and diazepam caused significant increases in latencies to convulsions and death. C. procera latex proteins (50 or 100mg/kg) and 2mg/kg diazepam caused a decrease in sleep latency and an increase in sleep time compared with the control group and groups treated with 5 or 10mg/kg. Our results suggest that C. procera latex proteins have a central nervous system-depressant activity as reflected in their potentiation of pentobarbital-induced sleeping time and their anticonvulsant action in the PTZ-induced seizure model.

The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson's disease: a review.

ABSTRACT This work reviews the evidence of the mechanism of neuronal degeneration in Parkinson's disease (PD) and the neuroprotective effect of lipoic acid and its use in the treatment of PD. PD is characterized by slow and progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta, leading to reduction of the striatal dopaminergic terminals. It is known that several factors influence neuronal damage. Among these factors, oxidative stress, immune system activity, microglial cells, and apoptotic mechanisms are of major importance. Currently, several antioxidants have been studied with the aim of reducing/slowing the progression of neurodegenerative processes. Lipoic acid is considered a universal antioxidant because it is an amphipathic substance. Lipoic acid and its reduced form, dihidrolipoic acid, act against reactive oxygen species, reducing oxidative stress. Therefore, this antioxidant has been used in the treatment of many diseases, including a new perspective for the treatment of Parkinson's disease.

Epidemiologia das infecções em queimaduras no nordeste do Brasil / Epidemiology of the infections in burns in the northeast of Brazil / Epidemiología de las infecciones en quemaduras en el nordeste de Brasil

As infecções hospitalares são complicações freqüentes, graves que comprometem a recuperação dos pacientes queimados. O presente estudo teve como objetivo identificar o perfil epidemiológico e os principais microrganismos isolados de infecções em vítimas de queimaduras em Fortaleza/CE. Estudo observacional, longitudinal, prospectivo, utilizando dados secundários dos indivíduos atendidos no Centro de Tratamento de Queimados (CTQ) do Instituto Dr. José Frota (IJF) para tratamento de queimaduras, atendidos entre janeiro/ 2004 a abril/2006. 419 vítimas de queimaduras foram atendidas no período estudado, sendo maioria do sexo masculino (59,43%), procedente de Fortaleza (56,80%), com menos de três anos de idade (30,31%). Do total, 188 pacientes (44,88%) apresentaram queimaduras em 11 a 20% da superfície corporal queimada (SCQ). Foram notificados 175 casos de infecções hospitalares, sendo a infecção da corrente sangüínea a mais prevalente (77,14%), seguida da infecção respiratória (11,43%), do trato urinário (8,0%) e cutânea (2,86%). Os microorganismos mais comumente isolados foram Staphylococcus aureus (34,69%), Pseudomonas sp.(33,33%), Enterobacter sp.(14,29%), Escherichia coli (4,08%) e Klebsiella pneumoniae (3,40%). A faixa etária mais acometida foi abaixo de três anos, evidencia necessidade dos pais assegurarem a segurança de seus filhos em casa. Os microorganismos isolados ratificam o risco elevado das vítimas de queimaduras as infecções endógenas e exógenas.

The hospital infections are frequent and serious complications that threaten the recovery of burned patients. Objectives: To identify the epidemiological profile and the main microorganisms isolated from infections in burned victims in Fortaleza/Ceará. Methodology: An observational study, longitudinal, prospective, using secondary data of individuals attended the Center for Treatment of Burns (CTQ) of the Institute Dr. Jose Frota (IJF) for treatment of burns, attended from January of 2004 to April of 2006. A total of 419 victims of burns was attended during the study period, the majority being male (59.43%), from Fortaleza (56.80%) and aged less than three years (30.31%). Of the total, 188 patients (44.88%) had burns from 11% to 20% of body surface area (SCQ). There were 175 cases of hospital infections, and the infection of the bloodstream was the most prevalent (77.14%), followed by respiratory infection (11.43%), urinary tract infection (8.0%) and skin (2, 86%). Staphylococcus aureus (34.69%), Pseudomonas sp. (33.33%), Enterobacter sp. (14.29%), Escherichia coli (4.08%) and Klebsiella pneumoniae (3, 40%) were isolated in the patients. Conclusion: The most of burn victims were children with less than three years old, highlighting the need for parents to ensure the safety of their children at home. The microorganisms isolated in the study group ratify the high risk of burns victims for acquiring exogenous and exogenous infections.

Las infecciones hospitalarias son complicaciones frecuentes, graves que perjudican la recuperación de los pacientes quemados. Objetivos: determinar el perfil epidemiológico de los pacientes víctimas de quemaduras; conocer los principales indicadores epidemiológicos de las infecciones hospitalarias y identificar los principales microorganismos aislados en las infecciones de los pacientes quemados. Metodología: Se trata de un estudio descriptivo, documental y de carácter retrospectivo. La muestra fue constituida por 419 pacientes quemados de los que 59,43% eran de sexo masculino y 40,57% femenino. Resultados: En cuanto a la procedencia 238, (56,80%) eran provenientes de la capital y 181, (43,20%) del interior. La franja de edad más afectada fue de 0 a 3 años con 127, (30,31%); 188 pacientes (44,88%) presentaron superficie corporal quemada (SCQ) entre 11 y 20%. Fueron notificados 175 casos de infecciones hospitalarias siendo la infección de la corriente sanguínea la más presente 135, (77,14%), seguida por la infección respiratoria 20, (11,43%), infección del trato urinario 14, (8,0%) y cutánea 05, (2,86%). Los microorganismos más comúnmente aislados fueron Staphylococcus aureus (34,69%), Pseudomonas sp.(33,33%), Enterobacter sp.(14,29%), Escherichia coli (4,08%) y Klebsiella pneumoniae (3,40%). Conclusiones: que la franja de edad mas afectada fue la de los niños, priorizando la seguridad dentro de la casa y atención de los padres, y que la instalación de patógenos de tamaña naturaleza ocurre debido a las condiciones favorables en que os pacientes quemados se encuentran.